Abstract:
Extracellular nucleotides are widely recognized as crucial modulators of immune responses in peripheral tissues. Adenosine triphosphate (ATP) and adenosine are key components of extracellular nucleotides, the balance of which contributes to immune homeostasis. Under tissue injury, ATP exerts its pro-inflammatory function, while the adenosinergic pathway rapidly degrades ATP to immunosuppressive adenosine, thus inhibiting excessive and uncontrolled inflammatory responses. Previous reviews have explored the immunoregulatory role of extracellular adenosine in various pathological conditions, especially inflammation and malignancy. However, current knowledge regarding adenosine and adenosinergic metabolism in the context of solid organ transplantation remains fragmented. In this review, we summarize the latest information on adenosine metabolism and the mechanisms by which it suppresses the effector function of immune cells, as well as highlight the protective role of adenosine in all stages of solid organ transplantation, including reducing ischemia reperfusion injury during organ procurement, alleviating rejection, and promoting graft regeneration after transplantation. Finally, we discuss the potential for future clinical translation of adenosinergic pathway in solid organ transplantation.
摘要:
细胞外核苷酸被广泛认为是外周组织中免疫应答的关键调节剂。ATP和腺苷是细胞外核苷酸的关键成分,其平衡有助于免疫稳态。在组织损伤下,ATP发挥其促炎功能,而腺苷途径迅速将ATP降解为免疫抑制腺苷,从而抑制过度和不受控制的炎症反应。以前的综述已经探讨了细胞外腺苷在各种病理条件下的免疫调节作用,尤其是炎症和恶性肿瘤。然而,在实体器官移植的背景下,关于腺苷和腺苷代谢的现有知识仍然支离破碎。在这次审查中,我们总结了腺苷代谢及其抑制免疫细胞效应功能的机制的最新信息,以及强调腺苷在实体器官移植各个阶段的保护作用,包括减少器官获取期间的缺血再灌注损伤(IRI),减轻拒绝,促进移植后的移植物再生。最后,我们讨论了在实体器官移植中腺苷途径的未来临床转化的潜力。